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Epileptic Disorders : International... Dec 2022We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants,...
We carried out a systematic review of published information on transfer of antiseizure medications (ASMs) into breastmilk, ASM serum concentrations in breastfed infants, and the wellbeing of infants breastfed by mothers on ASM treatment. Information was extracted from 85 relevant articles. No data on ASM levels in breastmilk or in breastfed infants was identified for cannabidiol, cenobamate, clobazam, eslicarbazepine-acetate, everolimus, felbamate, fenfluramine, retigabine, rufinamide, stiripentol, tiagabine, and vigabatrin. For ASMs, with available information on levels in breastfed infants, very low concentrations (in the order of 10% or less of maternal serum concentrations) were reported for carbamazepine, gabapentin, levetiracetam, oxcarbazepine, phenytoin, valproate, and clonazepam. Slightly higher levels (up to approximately 30% of maternal serum concentrations) have been observed with lamotrigine and topiramate, and in single case reports for brivaracetam, lacosamide, and perampanel. High infant levels (30% up to 100% of maternal serum concentrations) have been reported with ethosuximide, phenobarbital and zonisamide. Adverse infant effects during breastfeeding by mothers on ASMs appear to be rare regardless of the type of ASM, but systematic study is limited. Prospective long-term follow-up studies of developmental outcomes among children who have been breastfed by mothers taking ASMs are sparse and have mainly involved children whose mothers were taking carbamazepine, lamotrigine, levetiracetam, phenytoin or valproate as monotherapy while breastfeeding. Although these studies have not indicated poorer outcome among breastfed children compared with those who were not breastfed, further data on long-term outcomes are needed to draw firm conclusions. It is concluded that breastfeeding should in general be encouraged in women taking ASMs, given the well-established benefits of breastfeeding with regard to both short- and long-term infant health in the general population. Counselling needs to be individualized including information on the current knowledge regarding the woman's specific ASM treatment.
Topics: Breast Feeding; Cannabidiol; Carbamazepine; Child; Clobazam; Clonazepam; Epilepsy; Ethosuximide; Everolimus; Felbamate; Female; Fenfluramine; Gabapentin; Humans; Infant; Lacosamide; Lamotrigine; Levetiracetam; Oxcarbazepine; Phenobarbital; Phenytoin; Prospective Studies; Tiagabine; Topiramate; Valproic Acid; Vigabatrin; Zonisamide
PubMed: 36193017
DOI: 10.1684/epd.2022.1492 -
The Cochrane Database of Systematic... Apr 2015Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Cocaine dependence is a major public health problem that is characterised by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence, none is currently available for cocaine dependence, despite two decades of clinical trials primarily involving antidepressant, anticonvulsivant and dopaminergic medications. Extensive consideration has been given to optimal pharmacological approaches to the treatment of individuals with cocaine dependence, and both dopamine antagonists and agonists have been considered. Anticonvulsants have been candidates for use in the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction.
OBJECTIVES
To evaluate the efficacy and safety of anticonvulsants for individuals with cocaine dependence.
SEARCH METHODS
We searched the Cochrane Drugs and Alcohol Group Trials Register (June 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 6), MEDLINE (1966 to June 2014), EMBASE (1988 to June 2014), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to June 2014), Web of Science (1991 to June 2014) and the reference lists of eligible articles.
SELECTION CRITERIA
All randomised controlled trials and controlled clinical trials that focus on the use of anticonvulsant medications to treat individuals with cocaine dependence.
DATA COLLECTION AND ANALYSIS
We used the standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included a total of 20 studies with 2068 participants. We studied the anticonvulsant drugs carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate and vigabatrin. All studies compared anticonvulsants versus placebo. Only one study had one arm by which the anticonvulsant was compared with the antidepressant desipramine. Upon comparison of anticonvulsant versus placebo, we found no significant differences for any of the efficacy and safety measures. Dropouts: risk ratio (RR) 0.95, 95% confidence interval (CI) 0.86 to 1.05, 17 studies, 20 arms, 1695 participants, moderate quality of evidence. Use of cocaine: RR 0.92, 95% CI 0.84 to 1.02, nine studies, 11 arms, 867 participants, moderate quality of evidence; side effects: RR 1.39, 95% CI 1.01 to 1.90, eight studies, 775 participants; craving: standardised mean difference (SMD) -0.25, 95% CI -0.59 to 0.09, seven studies, eight arms, 428 participants, low quality of evidence.
AUTHORS' CONCLUSIONS
Although caution is needed when results from a limited number of small clinical trials are assessed, no current evidence supports the clinical use of anticonvulsant medications in the treatment of patients with cocaine dependence. Although the findings of new trials will improve the quality of study results, especially in relation to specific medications, anticonvulsants as a category cannot be considered first-, second- or third-line treatment for cocaine dependence.
Topics: Anticonvulsants; Cocaine-Related Disorders; Humans; Randomized Controlled Trials as Topic
PubMed: 25882271
DOI: 10.1002/14651858.CD006754.pub4 -
Clinical Pharmacology and Therapeutics Dec 2022The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics...
The objective of this study was to evaluate the evidence on cost-effectiveness of pharmacogenetic (PGx)-guided treatment for drugs with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. A systematic review was conducted using multiple biomedical literature databases from inception to June 2021. Full articles comparing PGx-guided with nonguided treatment were included for data extraction. Quality of Health Economic Studies (QHES) was used to assess robustness of each study (0-100). Data are reported using descriptive statistics. Of 108 studies evaluating 39 drugs, 77 (71%) showed PGx testing was cost-effective (CE) (N = 48) or cost-saving (CS) (N = 29); 21 (20%) were not CE; 10 (9%) were uncertain. Clopidogrel had the most articles (N = 23), of which 22 demonstrated CE or CS, followed by warfarin (N = 16), of which 7 demonstrated CE or CS. Of 26 studies evaluating human leukocyte antigen (HLA) testing for abacavir (N = 8), allopurinol (N = 10), or carbamazepine/phenytoin (N = 8), 15 demonstrated CE or CS. Nine of 11 antidepressant articles demonstrated CE or CS. The median QHES score reflected high-quality studies (91; range 48-100). Most studies evaluating cost-effectiveness favored PGx testing. Limited data exist on cost-effectiveness of preemptive and multigene testing across disease states.
Topics: Humans; Pharmacogenomic Testing; Pharmacogenetics; Cost-Benefit Analysis; Warfarin; Carbamazepine
PubMed: 36149409
DOI: 10.1002/cpt.2754 -
International Journal of Environmental... Jan 2021Cerebellar degeneration has been associated in patients with epilepsy, though the exact pathogenic mechanisms are not understood. The aim of this systematic review was... (Review)
Review
INTRODUCTION
Cerebellar degeneration has been associated in patients with epilepsy, though the exact pathogenic mechanisms are not understood. The aim of this systematic review was to identify the prevalence of cerebellar degeneration in patients with epilepsy and identify any pathogenic mechanisms.
METHODOLOGY
A systematic computer-based literature search was conducted using the PubMed database. Data extracted included prevalence, clinical, neuroradiological, and neuropathological characteristics of patients with epilepsy and cerebellar degeneration.
RESULTS
We identified three consistent predictors of cerebellar degeneration in the context of epilepsy in our review: temporal lobe epilepsy, poor seizure control, and phenytoin as the treatment modality. Whole brain and hippocampal atrophy were also identified in patients with epilepsy.
CONCLUSIONS
Cerebellar degeneration is prevalent in patients with epilepsy. Further prospective studies are required to confirm if the predictors identified in this review are indeed linked to cerebellar degeneration and to establish the pathogenic mechanisms that result in cerebellar insult.
Topics: Atrophy; Brain; Epilepsy; Epilepsy, Temporal Lobe; Humans; Magnetic Resonance Imaging; Prospective Studies
PubMed: 33435567
DOI: 10.3390/ijerph18020473 -
The Cochrane Database of Systematic... Sep 2021This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures.... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in 2014. Epilepsy is a common neurological condition characterised by recurrent seizures. Pharmacological treatment remains the first choice to control epilepsy. Sulthiame (STM) is widely used as an antiepileptic drug in Europe and Israel. In this review, we have presented a summary of evidence for the use of STM as monotherapy in epilepsy.
OBJECTIVES
To assess the efficacy and side effect profile of STM as monotherapy when compared with placebo or another antiepileptic drug for people with epilepsy.
SEARCH METHODS
We searched the following databases on 13 April 2020: the Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 10 April 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Cochrane Epilepsy. We imposed no language restrictions. We contacted the manufacturers of STM and researchers in the field to ask about ongoing and unpublished studies.
SELECTION CRITERIA
Randomised controlled monotherapy trials of STM in people of any age with epilepsy of any aetiology.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology. Two review authors independently selected trials for inclusion and extracted the relevant data. We assessed the following outcomes: treatment withdrawal; seizure-free at six months; adverse effects; and quality of life scoring. We conducted the primary analyses by intention-to-treat where possible, and presented a narrative analysis of the data.
MAIN RESULTS
We included four studies involving a total of 355 participants: three studies (209 participants) with a diagnosis of benign epilepsy of childhood with centrotemporal spikes (BECTS), and one study (146 participants) with a diagnosis of generalised tonic-clonic seizures (GTCS). STM was given as monotherapy compared with placebo and with levetiracetam in the BECTS studies, and compared with phenytoin in the GTCS study. An English translation of the full text of one of the BECTS studies could not be found, and analysis of this study was based solely on the English translation of the abstract. For the primary outcome, the total number of dropouts caused either by seizure recurrence or adverse reaction was significantly higher in the levetiracetam treatment arm compared to the STM treatment arm (RR 0.32, 95% Cl 0.10 to 1.03; 1 study, 43 participants; low-certainty evidence). For the secondary outcomes for this comparison, results for seizure freedom were inconclusive (RR 1.12, 95% Cl 0.88 to 1.44; 1 study, 43 participants; low-certainty evidence). Reporting of adverse effects was incomplete. Participants receiving STM were significantly less likely to develop gingival hyperplasia than participants receiving phenytoin in the GTCS study (RR 0.03, 95% CI 0.00 to 0.58; 1 study, 146 participants; low-certainty evidence). No further statistically significant adverse events were noted when STM was compared with phenytoin or placebo. The most common adverse events were related to behavioural disturbances when STM was compared with levetiracetam (RR 0.95, 95% Cl 0.59 to 1.55; 1 study, 43 participants; low-certainty evidence), with the same incidence in both groups. No data were reported for quality of life. Overall, we assessed one study at high risk of bias and one study at unclear bias across the seven domains, mainly due to lack of information regarding study design. Only one trial reported effective methods for blinding. The risk of bias assessments for the other two studies ranged from low to high. We rated the overall certainty of the evidence for the outcomes as low using the GRADE approach.
AUTHORS' CONCLUSIONS
This review provides insufficient information to inform clinical practice. Small sample sizes, poor methodological quality, and lack of data on important outcome measures precluded any meaningful conclusions regarding the efficacy and tolerability of sulthiame as monotherapy in epilepsy. More trials, recruiting larger populations, over longer periods, are needed to determine whether sulthiame has a clinical use.
Topics: Anticonvulsants; Epilepsy; Humans; Quality of Life; Randomized Controlled Trials as Topic; Thiazines
PubMed: 34554571
DOI: 10.1002/14651858.CD010062.pub3 -
Seizure Oct 2021We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted... (Review)
Review
BACKGROUND
We systematically reviewed the existing literature on the cosmetic adverse effects of antiseizure medications (ASMs) in order to depict a clear picture of these unwanted side effects of ASMs with a particular attention to hair loss, hirsutism, acne, and gingival hyperplasia.
METHODS
This systematic review was prepared according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Scopus, MEDLINE, and Google Scholar from the inception to 25 March, 2021 were systematically searched. These key words (title/abstract) were used: "hair loss" OR "hirsutism" OR "acne" OR "gingival hyperplasia" AND "seizure" OR "epilepsy" OR "anriseizure" OR "antiepileptic". The exclusion criteria included: non-original studies, articles not in English, and animal studies.
RESULTS
The primary search yielded 3938 studies; 127 studies were related to the topic and were included in the current systematic review. The most robust evidence on cosmetic adverse effects of ASMs were related to phenytoin (causing gingival hyperplasia, hirsutism, and acne) and valproate (causing hair loss and hirsutism); however, many other ASMs were also implicated in causing these cosmetic adverse effects.
CONCLUSION
Antiseizure medications may be associated with various cosmetic adverse effects. Phenytoin and valproate are the most notorious ASMs in this regard; but, other ASMs have also been implicated in causing hair loss, hirsutism, acne, and gingival hyperplasia. Physicians should pay more attention to these significant adverse effects that may affect a patient's facial attractiveness, quality of life, and emotional state.
Topics: Animals; Anticonvulsants; Epilepsy; Humans; Phenytoin; Quality of Life; Valproic Acid
PubMed: 34052629
DOI: 10.1016/j.seizure.2021.05.010 -
Neurologia May 2023No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
No formal indication currently exists for seizure prophylaxis in neurosurgical oncology patients. Neither have specific recommendations been made on the use of antiepileptic drugs (AED) in seizure-free patients with meningiomas scheduled for surgery. AEDs are generally prescribed on a discretionary basis, taking into consideration a range of clinical and radiological risk factors. We present a systematic review and meta-analysis exploring the effectiveness of antiepileptic prophylaxis in patients with meningioma and no history of seizures.
METHODS
We performed a systematic review of the PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, and clinicaltrials.gov databases. Of a total of 4368 studies initially identified, 12 were selected for extraction of data and qualitative analysis. Based on the clinical data presented, we were only able to include 6 studies in the meta-analysis. We performed heterogeneity studies, calculated a combined odds ratio, evaluated publication bias, and conducted a sensitivity analysis.
RESULTS
AED prophylaxis in patients with meningioma and no history of seizures did not significantly reduce the incidence of post-operative seizures in comparison to controls (Mantel-Haenszel combined odds ratio, random effects model: 1.26 [95% confidence interval, 0.60-2.78]; 2041 patients). However, we are unable to establish a robust recommendation against this treatment due to the lack of prospective studies, the presence of selection bias in the studies reviewed, the likelihood of underestimation of seizure frequency during follow-up, and the strong influence of one study on the overall effect.
CONCLUSIONS
Despite the limitations of this review, the results of the meta-analysis do not support the routine use of seizure prophylaxis in patients with meningioma and no history of seizures.
Topics: Humans; Meningioma; Phenytoin; Anticonvulsants; Incidence; Meningeal Neoplasms
PubMed: 35781420
DOI: 10.1016/j.nrleng.2022.03.002 -
Seizure Sep 2015Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in adults for status epilepticus (SE) and refractory status epilepticus... (Review)
Review
INTRODUCTION
Our goal was to perform a systematic review of the literature on the use of intravenous lidocaine in adults for status epilepticus (SE) and refractory status epilepticus (RSE) to determine its impact on seizure control.
METHODS
All articles from MEDLINE, BIOSIS, EMBASE, Global Health, HealthStar, Scopus, Cochrane Library, the International Clinical Trials Registry Platform (inception to November 2014), and gray literature were searched. The strength of evidence was adjudicated using both the Oxford and GRADE methodology by two independent reviewers.
RESULTS
Overall, 13 studies were identified, with 11 manuscripts and 2 meeting abstracts. Seventy-six adult patients were treated for 82 episodes of SE/RSE. Patients had varying numbers of anti-epileptic drugs (AEDs), 1-12, on board prior to lidocaine therapy. During 69 of the 82 (84.1%) episodes of SE/RSE, phenytoin was on board. The dose regimen of lidocaine varied, with some utilizing bolus dosing alone; others utilizing a combination of bolus and infusion therapy. Overall, 70.7% of seizures responded to lidocaine, with complete cessation and greater than 50% reduction seen in 64.1% and 6.1% respectively. Patient outcomes were sparingly reported.
CONCLUSIONS
There currently exists level 4, GRADE C evidence to support the consideration of lidocaine for SE and RSE in the adult population. Thus there is currently weak evidence to support the use of lidocaine in this context. Further prospective studies of lidocaine administration in this setting are warranted.
Topics: Adult; Anticonvulsants; Humans; Lidocaine; Seizures; Status Epilepticus
PubMed: 26362376
DOI: 10.1016/j.seizure.2015.07.003 -
The Cochrane Database of Systematic... Jul 2018This is an updated version of the original Cochrane Review published in Issue 10, 2014. There is a need to expand monotherapy options available to a clinician for the... (Review)
Review
BACKGROUND
This is an updated version of the original Cochrane Review published in Issue 10, 2014. There is a need to expand monotherapy options available to a clinician for the treatment of new focal or generalized seizures. A Cochrane systematic review for clobazam monotherapy is expected to define its place in the treatment of new-onset or untreated seizures and highlight gaps in evidence.
OBJECTIVES
To evaluate the efficacy, effectiveness, tolerability and safety of clobazam as monotherapy in people with new-onset focal or generalized seizures.
SEARCH METHODS
For the latest update we searched the following databases on 19 March 2018: the Cochrane Register of Studies (CRS Web), which includes the Cochrane Epilepsy Group Specialized Register and the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid, 1946- ), BIOSIS Previews (1969- ), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP). There were no language restrictions.
SELECTION CRITERIA
Randomized or quasi-randomized controlled trials comparing clobazam monotherapy versus placebo or other anti-seizure medication in people with two or more unprovoked seizures or single acute symptomatic seizure requiring short-term continuous anti-seizure medication, were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
Primary outcome measure was time on allocated treatment (retention time), reflecting both efficacy and tolerability. Secondary outcomes included short- and long-term effectiveness measures, tolerability, quality of life, and tolerance measures. Two authors independently extracted the data.
MAIN RESULTS
We identified three trials fulfilling the review criteria, which included 206 participants. None of the identified studies reported the preselected primary outcome measure. A meta-analysis was not possible. Lack of detail regarding allocation concealment and a high risk of performance and detection bias in two studies prompted us to downgrade the quality of evidence (by using the GRADE approach) for some of our results due to risk of bias.Regarding retention at 12 months, we detected no evidence of a statistically significant difference between clobazam and carbamazepine (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.61 to 1.12; low-quality evidence). There was low-quality evidence that clobazam led to better retention compared with phenytoin (RR 1.43, 95% CI 1.08 to 1.90). We could not determine whether participants receiving clobazam were found to be less likely to discontinue it due to adverse effects as compared to phenytoin (RR 0.10, 95% CI 0.01 to 1.65, low-quality evidence).
AUTHORS' CONCLUSIONS
We found no advantage for clobazam over carbamazepine for retention at 12 months in drug-naive children and a slight advantage of clobazam over phenytoin for retention at six months in adolescents and adults with neurocysticercosis in a single clinical trial each. At present, the available evidence is insufficient to inform clinical practice.
Topics: Adolescent; Adult; Anticonvulsants; Benzodiazepines; Carbamazepine; Child; Clobazam; Epilepsies, Partial; Epilepsy, Generalized; Humans; Phenytoin; Randomized Controlled Trials as Topic; Seizures
PubMed: 29995989
DOI: 10.1002/14651858.CD009258.pub3 -
Neurology Jan 2023Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a...
BACKGROUND AND OBJECTIVES
Early life epilepsies are common and often debilitating, but no evidence-based management guidelines exist outside of those for infantile spasms. We conducted a systematic review of the effectiveness and harms of pharmacologic and dietary treatments for epilepsy in children aged 1-36 months without infantile spasms.
METHODS
We searched EMBASE, MEDLINE, PubMed, and the Cochrane Library for studies published from January 1, 1999, to August 19, 2021. Using prespecified criteria, we identified studies reporting data on children aged 1-36 months receiving pharmacologic or dietary treatments for epilepsy. We did not require that studies report etiology-specific data. We excluded studies of neonates, infantile spasms, and status epilepticus. We included studies administering 1 of 29 pharmacologic treatments and/or 1 of 5 dietary treatments reporting effectiveness outcomes at ≥ 12 weeks. We reviewed the full text to find any subgroup analyses of children aged 1-36 months.
RESULTS
Twenty-three studies met inclusion criteria (6 randomized studies, 2 nonrandomized comparative studies, and 15 prestudies/poststudies). All conclusions were rated low strength of evidence. Levetiracetam leads to seizure freedom in some infants (32% and 66% in studies reporting seizure freedom), but data on 6 other medications were insufficient to permit conclusions about effectiveness (topiramate, lamotrigine, phenytoin, vigabatrin, rufinamide, and stiripentol). Three medications (levetiracetam, topiramate, and lamotrigine) were rarely discontinued because of adverse effects, and severe events were rare. For diets, the ketogenic diet leads to seizure freedom in some infants (rates 12%-37%), and both the ketogenic diet and modified Atkins diet reduce average seizure frequency, but reductions are greater with the ketogenic diet (1 RCT reported a 71% frequency reduction at 6 months for ketogenic diet vs only a 28% reduction for the modified Atkins diet). Dietary harms were not well-reported.
DISCUSSION
Little high-quality evidence exists on pharmacologic and dietary treatments for early life epilepsies. Future research should isolate how treatments contribute to outcomes, conduct etiology-specific analyses, and report patient-centered outcomes such as hospitalization, neurodevelopment, functional performance, sleep quality, and patient and caregiver quality of life.
TRIAL REGISTRATION INFORMATION
This systematic review was registered in PROSPERO (CRD42021220352) on March 5, 2021.
Topics: Infant; Infant, Newborn; Child; Humans; Lamotrigine; Levetiracetam; Topiramate; Spasms, Infantile; Quality of Life; Epilepsy; Anticonvulsants; Diet, Ketogenic
PubMed: 36270899
DOI: 10.1212/WNL.0000000000201026